ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.2179C>T (p.Arg727Ter)

gnomAD frequency: 0.00001  dbSNP: rs376667075
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817435 SCV000957995 pathogenic not provided 2024-12-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg727*) in the MSH3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH3 are known to be pathogenic (PMID: 27476653, 37402566). This variant is present in population databases (rs376667075, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 660274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002427027 SCV002727300 pathogenic Hereditary cancer-predisposing syndrome 2023-12-19 criteria provided, single submitter clinical testing The p.R727* pathogenic mutation (also known as c.2179C>T), located in coding exon 15 of the MSH3 gene, results from a C to T substitution at nucleotide position 2179. This changes the amino acid from an arginine to a stop codon within coding exon 15. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003458547 SCV004189073 pathogenic Familial adenomatous polyposis 4 2023-08-30 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics RCV003461246 SCV004197504 likely pathogenic Endometrial carcinoma 2022-08-25 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000817435 SCV005436381 pathogenic not provided 2024-11-01 criteria provided, single submitter clinical testing MSH3: PVS1, PM2

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